Diisopropylamine → Disoxaril

HRID 359808Notes

Reaction equation

HRID 359808 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[CH:18]=[C:17]([CH3:19])[O:16][N:15]=1.Br[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[O:35][CH2:36][CH2:37][N:38]=2)=[CH:30][CH:29]=1>O1CCCC1.CCCCCC.O>[O:35]1[CH2:36][CH2:37][N:38]=[C:34]1[C:31]1[CH:32]=[CH:33][C:28]([O:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:19][C:17]2[O:16][N:15]=[C:14]([CH3:13])[CH:18]=2)=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 93123,5-DimethylisoxazoleHCID 20063999HCID 20063999, compoundHCID 178418339Butyllithium

Product 1

HCID 55717Disoxaril

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred solution of 6.0 ml of diisopropylamine in 50 ml of tetrahydrofuran at 0° C. was added 22 ml of 2.1M n-butyllithium in hexane over a period of 20 minutes. The mixture was stirred 30 minutes at 5° C., then cooled to -55° C., and 4.5 g of 3,5-dimethylisoxazole was added dropwise during 15 minutes. The resulting slurry was stirred for 30 minutes at -60° C. and 12.4 g of 2-[4-(6-bromohexyloxy)phenyl]-4,5-dihydro-oxazole in 35 ml of tetrahydrofuran was then added dropwise. After the addition was complete, the mixture was stirred for one hour during which the temperature rose to -40° C. The reaction mixture was allowed to warm to room temperature, 75 ml of water was then added dropwise, and the mixture was extracted with ethyl acetate. The ethyl acetate extracts were dried and concentrated in vacuo, and the residue triturated with ether. The ether insoluble fraction (10.5) consisted essentially of 5-{7-[4-(4,5-dihydro-2-oxazolyl)phenoxy]heptyl}-3-methylisoxazole, identical with the product of Example 1, part (c).

Workup

  1. temperaturecooled to -55° C.
  2. stirringThe resulting slurry was stirred for 30 minutes at -60° C.
  3. additionAfter the addition
  4. stirringthe mixture was stirred for one hour during which the temperature
  5. customrose to -40° C
  6. temperatureto warm to room temperature
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe ethyl acetate extracts were dried
  9. concentrationconcentrated in vacuo
  10. customthe residue triturated with ether

Sources & evidence

ORD record
ord-c3106739a4fa4534b467823ce438f528
Source dataset
uspto-grants-1991_03
Patent number
US05002960

Reaction notes

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